This project is designed to prepare a GMP quality investigational HIV vaccine and complete the preclinical and laboratory studies needed for clinical studies of a multicomponent HIV-1 adenoviral vector vaccine. The hypothesis is that the vaccine will be safe for human administration and elicit immune responses to HIV-1. Subjects receive adenovector vaccine either as a single agent or as a boost after priming with plasmid DNA vaccines. The Vaccine Research Center (VRC), NIAID is developing a novel prime-boost HIV vaccine strategy directed at the three most globally prevalent HIV subtypes (clades). VRC's HIV prime-boost candidate is designed to elicit immune responses to HIV sequences from clades A, B and C which together cause about 90 percent of incident HIV infections around the world. In November 2004, the VRC Clinical Trials Core launched a Phase I clinical study (VRC 006) of a multiclade, multigene recombinant adenovector 5 vaccine at the NIH Clinical Center (Bethesda, MD) as the first step in developing the prime-boost regimen. This product has since been evaluated clinically as a single agent and as part of a DNA prime-adenovector boost regimen in several Phase 1 and 2 clinical trials in U.S. and international sites. Production of Phase II materials has been completed. Additional new serotype adeno vectors are in development for production.